Summary- Substantial progress was made on this project, with four original research articles published. In particular, we described the pharmacology of ()-cis-para-methyl-4-methylaminorex (4,4-DMAR), a designer drug associated with nearly twenty deaths in Europe. Our data demonstrate that 4,4-DMAR is being sold over the Internet under the name Serotoni, and the drug is a powerful monoamine releasing agent similar to 3,4-methylenedioxmethamphetamine (MDMA). Characterization of a novel and potentially lethal designer drug ()-cis-para-methyl-4-methylaminorex (4,4'-DMAR, or 'Serotoni') (2014) Brandt SD, Baumann MH, Partilla JS, et al. Drug Test Analysis 6:684-95. During the second half of 2013, a total of 26 deaths involving para-methyl-4-methylaminorex (4,4'-DMAR) were reported to the European Monitoring Centre for Drugs and Drug Addiction. While aminorex and 4-methylaminorex (4-MAR) are known psychostimulants, nothing is known about the comparatively new para-methyl analog. Analytical characterization of two independent samples obtained from online vendors confirmed the presence of the ()-cis isomer that also appeared to be associated with at least 18 of the 26 deaths. Extensive characterizations included crystal structure analysis, single, tandem, and high-resolution mass spectrometry, liquid and gas chromatography, and nuclear magnetic resonance spectroscopy. For the work described here, both the ()-cis and ()-trans racemates were also synthesized, confirming that the differentiation between these two forms was straight-forward. Monoamine transporter activity was studied using rat brain synaptosomes which included the comparison with d-amphetamine, aminorex and ()-cis-4-MAR. ()-cis-4,4'-DMAR was a potent, efficacious substrate-type releaser at transporters for dopamine, norepinephrine and serotonin with EC50 values of 8.6&#8201;&#8201;1.1 nM (DAT), 26.9&#8201;&#8201;5.9 nM (NET) and 18.5&#8201;&#8201;2.8 nM (SERT), respectively. The potency of ()-cis-4,4'-DMAR at DAT and NET rivalled that of other psychomotor stimulant drugs like d-amphetamine and aminorex. However, ()-cis-4,4'-DMAR had much more potent actions at SERT and activity at SERT varied more than 100-fold across the four drugs. The potent releasing activity of ()-cis-4,4'-DMAR at all three monoamine transporters predicts a potential for serious side-effects such as psychotic symptoms, agitation, hyperthermia and cardiovascular stimulation, especially after high-dose exposure or following combination with other psychostimulants.